由于黑色素瘤的侵袭性和复发性特征，为治愈该病通常需要多次、多模式的治疗。微针（MN）基于经皮给药方法可以使药物避免一过性代谢和克服角质层屏障，但这些给药方法的主要挑战在于缺乏可控的药物释放/激活和有效的成像方法来指导整个治疗过程。为实现具有可控药物释放/激活和有效成像引导的经皮给药方法，我们设计了一种近红外（NIR）光致活性、可溶解的微针系统，包括含有共载有光敏剂吲哚菁绿（ICG）和反应氧化物种激活的Doxorubicin（pB-DOX）的脂质体的可溶解聚乙烯吡咯烷酮微针组（MN-pB/I)。将微针贴片贴到肿瘤部位后，浓集在针尖的脂质体在基质溶解后释放到肿瘤组织中，在定位输送后可被均匀分布。然后，经过近红外光照射后由ICG产生的ROS将执行光动力学疗法，并通过裂解前药基团将pB-DOX转化为DOX用于化疗。ICG作为一种染料也用于通过荧光和光声成像指导治疗方案和监测疗效。 MN-pB / I 组的肿瘤生长被抑制了 93.5%，而对照组仅被部分抑制。观察到几乎没有治疗引起的副作用和心脏毒性。 MN-pB / I代表一种多模式、生物相容的治疗系统，具有时空控制功能，经过单次剂量即可消融黑色素瘤，是临床黑色素瘤治疗的有前途的候选方案。©2023.作者。

As a consequence of the aggressive and recurrent nature of melanoma, repeated, multimodal treatments are often necessary to cure the disease. While microneedle (MN)-based transdermal drug delivery methods can allow drugs to avoid first-pass metabolism and overcome the stratum corneum barrier, the main challenges of these delivery methods entail the lack of controlled drug release/activation and effective imaging methods to guide the entire treatment process.To enable a transdermal delivery method with controllable drug release/activation and effective imaging guidance, we designed a near-infrared (NIR) photoactivatable, dissolving MN system comprising dissolvable polyvinylpyrrolidone MNs arrays (MN-pB/I) containing liposomes that were co-loaded with the photosensitizer indocyanine green (ICG) and the reactive oxygen species (ROS)-activatable prodrug of doxorubicin (pB-DOX).After applying the MN patch to the tumor site, the liposomes concentrated in the needle tips were released into the tumor tissue and distributed evenly upon dissolution of the matrix to enable targeted delivery. Then, the ROS produced by ICG after exposure to NIR light performed photodynamic therapy and activated the pB-DOX for chemotherapy by cleaving the prodrug moiety and converting it to DOX. As a dye, ICG was also used to guide the treatment regimens and monitor the efficacy by fluorescence and photoacoustic imaging. The growth of the tumors in the MN-pB/I group were inhibited by 93.5%, while those were only partially inhibited in the control groups. Negligible treatment-induced side effects and cardiotoxicity were observed.The MN-pB/I represents a multimodal, biocompatible theragnostic system with spatiotemporal control that was capable of ablating melanoma tumors after a single dose, providing a promising candidate for clinical melanoma therapy.© 2023. The Author(s).